Zhang, Wen, Ge, Meng-meng, Zhang, Long-Qing and Manyande, Anne ORCID: https://orcid.org/0000-0002-8257-0722 (2022) Dysfunction of the Brain-derived Neurotrophic Factor-Tyrosine Kinase B Signaling Pathway Contributes to Learning and Memory Impairments Induced by Neuroinflammation in Mice. Neuroscience, 505. pp. 21-33.

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Abstract

Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF-TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). Western blotting was performed to elucidate roles of the BDNF-TrkB signaling pathway and its downstream cascades in LPS mice. The NORT showed that LPS induced learning and memory deficits in mice. The levels of IL-1β, IL-6, and TNF-α in the serum and central nervous system decreased in LPS mice. In addition, LPS reduced the protein levels of BDNF, p-TrkB, Bcl-2, p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 and increased the expression of Bax in the hippocampus and medial prefrontal cortex regions. In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF-TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases.

Item Type:	Article
Identifier:	10.1016/j.neuroscience.2022.10.003
Subjects:	Medicine and health
Depositing User:	Marc Forster
Date Deposited:	11 Apr 2024 08:03
Last Modified:	11 Apr 2024 08:03
URI:	https://repository.uwl.ac.uk/id/eprint/11431

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